The numbers and ratios of different lymphocyte subsets infiltrated into a disease-affected tissue, such as a solid tumor, often bears on the prognosis of the disease, e.g. Deschoolmeester et al, BMC immunology, 11:19 (2010); Obtain, Cancer Immunity, 7: 4 (2007); Yu et al. Laboratory investigation, 86: 233-245 (2006); Diederichsen et al. Cancer Immunol. Immmunother., 52:423-428 (2003); and the like. Unfortunately, measurement of such quantities using available technologies, such as immunohistochemistry or flow cytometry, is difficult, labor intensive, and not amenable for routine deployment.
Separately, there has been more and more interest in the use of large-scale DNA sequencing in diagnostic and prognostic applications as the per-base cost of DNA sequencing has dropped. For example, profiles of nucleic acids encoding immune molecules, such, as T cell or B cell receptors, or their components, contain a wealth of information on the state of health or disease of an organism, so that the use of such profiles as diagnostic or prognostic indicators has been proposed for a wide variety of conditions, e.g. Faham and Willis, U.S. patent publication 2910/0151471; Freeman et al. Genome Research, 19: 1817-1824 (2009); Boyd et al, Sci. Transl. Med., 1(12); 12ra23 (2009); He et al Oncotarget (Mar. 8, 2011).
If would be highly useful to the medical and scientific fields if the improvements in high throughput nucleic acid sequencing could be put to use to provide a more convenient and more effective assay for measuring tissue-infiltrating lymphocytes (TILs).